The present invention generally relates to enhancing the biocompatibility of polymeric surfaces as well as to medical devices or the like which include such biocompatibility-enhanced surfaces. More particularly, the invention relates to surface activation of polymeric surfaces by radiofrequency plasma treatment for the immobilization of anti-thrombogenic agents or the like on the polymeric surfaces. The radiofrequency plasma medium is one including water vapor in substantial concentrations, which medium when subjected to radiofrequency plasma discharge conditions activates the polymeric surface for attachment thereto of anti-thrombogenic agents such as heparinous materials and the like.
It is of course well known that it is important for many medical devices to have surfaces which are of enhanced biocompatibility. It is also well known that, generally speaking, biocompatibility properties are enhanced by attempting to secure anti-thrombogenic agents to polymeric surfaces of medical devices, particularly those which are blood contacting surfaces to be implanted or otherwise used during medical procedures and the like. In many instances, it is particularly undesirable to have the anti-thrombogenic agent leach away in wet environments such as are encountered by medical devices that engage blood or other body fluids.
Certain attempts have been made and approaches have been suggested whereby a polymeric surface is activated by treatment with a plasma which in turn reacts with heparin or the like to provide a polymeric surface having anti-thrombogenic properties. Included are patents incorporating plasma discharge treatment with a gaseous environment including a variety of gases, including inert gases and organic gases. Patents in this regard include U.S. Pat. Nos. 4,613,517, 4,656,083 and 4,948,628, which mention a variety of plasma media including those generated from hydrogen, helium, ammonia, nitrogen, oxygen, neon, argon, krypton, xenon, ethylenic monomers and other hydrocarbons, halohydrocarbons, halocarbons and silanes. It will be appreciated that various ones of these plasma media are relatively expensive and can be hazardous to use within a manufacturing environment and/or to dispose of as waste. Also, certain plasma media are more suitable for treatment of specific substrates.
Other surface treatments have been proposed that are said to activate polymeric surfaces for immobilization of anti-thrombogenic agents. Included are procedures which incorporate chromic acid treatments or flame oxidation procedures. Approaches of this type tend to be especially suitable for particular polymeric surfaces but not for others, and they can adversely affect the bulk properties of the polymeric material thus treated. Procedures of this general type have further disadvantages in that the particular geometry of the medical device or the like being treated must be taken into consideration in order to reach the surfaces requiring treatment.
It is desirable to provide a surface treatment procedure which is available for use in connection with rendering anti-thrombogenic any of a number of surfaces of medical devices or the like. It is further desirable that any plasma deposition procedure included in this regard avoid the need to use plasma media that are expensive, potentially hazardous or otherwise difficult to handle. At the same time, any plasma media should strongly bind the anti-thrombogenic agent to the surface being treated, preferably while also accomplishing this in an especially efficient manner that is readily susceptible to use on a large scale.
It has been discovered that plasma media which include a substantial concentration of water vapor, either alone or in combination with oxygen gas, provide an especially advantageous activation of numerous polymeric surfaces that are subjected to radiofrequency plasma treatment conditions in the environment of these media. A particularly simplified and efficient surface activation is achieved when the thus activated surface is treated with a spacer component having amine moieties, particularly spacer components which have primary or secondary amine groups. An anti-thrombogenic agent or the like, typically with the assistance of a coupling agent, is covalently bound to the spacer component. The result is an evenly covered biocompatible surface that significantly avoids leaching of the anti-thrombogenic agent or the like away from the medical device or the like.
It is accordingly a general object of the present invention to provide an improved method for treating polymeric surfaces and medical articles or the like having such surfaces.
Another object of the present invention is to provide improved medical device components having polymeric surfaces with anti-thrombogenic agents or the like immobilized thereon.
Another object of this invention is to provide an improved anti-thrombogenic polymeric surface and method of making same which utilizes radiofrequency plasma discharge techniques that avoid the use of expensive or hazardous plasma media.
Another object of the present invention is to provide an improved method for covalently binding anti-thrombogenic agents or the like to polymeric surfaces, which agents do not leach away in wet environments, as well as to the improved polymeric surfaces thus produced.
Another object of this invention is to provide an improved process for rendering medical device polymeric surfaces anti-thrombogenic through a process that is relatively independent of the particular polymeric surface and of the shape or geometry thereof.
These and other objects, features and advantages of this invention will be clearly understood through a consideration of the following detailed description.